Cannabinoid receptor antagonists
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Claims
1. A method of antagonising one or more of the actions of anandamide at cannabinol-1 receptors in a mammal, which comprises administering an effective amount of a compound of formula ##STR9## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
2. A method as claimed in claim 1, in which R.sup.2 is methyl or methoxy and R.sup.3 is methoxy.
3. A method as claimed in claim 2, in which R.sup.1 is methoxy, trifluoromethylsulfonyloxy, hydroxy or cyano.
4. A method as claimed in claim 3, in which R.sup.1 is cyano.
5. A method as claimed in claim 4, in which R.sup.2 is methoxy and R.sup.5 is --O--.
6. A method as claimed in claim 4, in which R.sup.2 is methyl and R.sup.5 is --O--.
7. A method as claimed in claim 4, in which R.sup.2 is methoxy and R.sup.5 is --S--.
8. A method of claim 1 wherein the action involves inhibiting neurotransmission by a cannabinoid receptor in a mammal by administering to said mammal an effective amount of a compound of formula ##STR10## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
9. A method of claim 1 wherein the action involves treating depression in a mammal by administering to said mammal an effective amount of a compound of formula ##STR11## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
10. A method of claim 1 wherein the action involves enhancing memory in a mammal by administering to a mammal an effective amount of a compound of formula ##STR12## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
11. A method of claim 1 wherein the action involves increasing alertness in a mammal by administering to a mammal an effective amount of a compound of formula ##STR13## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
12. A method of claim 1 wherein the action involves increasing sensory perception in a mammal by administering to a mammal an effective amount of a compound of formula ##STR14## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
13. A method of claim 1 wherein the action involves increasing cognitive function in a mammal by administering to a mammal an effective amount of a compound of formula ##STR15## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
14. A method of claim 1 wherein the action involves decreasing hallucinatory dementia in a mammal by administering to a mammal an effective amount of a compound of formula ##STR16## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
15. A method of claim 1 wherein the action involves treating drug induced schizophrenia, which comprises administering to a mammal an effective amount of a compound of formula ##STR17## in which: R.sup.1 is C.sub.1 -C.sub.4 alkoxy, trifluoromethylsulfonyloxy, hydroxy or cyano;
- R.sup.2 and R.sup.3 are each independently C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- R.sup.4 is CO, CHOH or CH.sub.2; and
- R.sup.5 is O or S, provided that when R.sup.1 is hydroxy, R.sup.5 is O.
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WO 95/10513 | April 1995 | WOX |
Type: Grant
Filed: Sep 30, 1996
Date of Patent: May 5, 1998
Assignee: Eli Lilly and Company (Indianapolis, IN)
Inventors: George J. Cullinan (Trafalgar, IN), Kennan J. Fahey (Indianapolis, IN), Gary A. Koppel (Indianapolis, IN)
Primary Examiner: Deborah Lambkin
Attorneys: Martin A. Hay, David E. Boone
Application Number: 8/724,101
International Classification: A61K 3138;